An Open-Label, Multi-Dose Efficacy and Safety Study of Intramuscular Tetrodotoxin in Patients with Severe Cancer-Related Pain  Neil A. Hagen, MD, FRCPC, Kim M. Fisher, PhD, Bernard Lapointe, MD, Patrick du Souich, MD, PhD, Srini Chary, MD, Dwight Moulin, MD, FRCPC, Ed Sellers, MD, PhD, FRCPC, Anh Ho Ngoc, PhD  Journal of Pain and Symptom Management  Volume 34, Issue 2, Pages 171-182 (August 2007) DOI: 10.1016/j.jpainsymman.2006.11.008 Copyright © 2007 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 1 Summary of the intent-to-treat (ITT) patient population. Journal of Pain and Symptom Management 2007 34, 171-182DOI: (10.1016/j.jpainsymman.2006.11.008) Copyright © 2007 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 2 Number of reports of gastrointestinal, nausea, nervous system, and most common (hypesthesia and parethesia) adverse effects (AE) as a function of tetrodotoxin dose. Journal of Pain and Symptom Management 2007 34, 171-182DOI: (10.1016/j.jpainsymman.2006.11.008) Copyright © 2007 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 3 Number of patients with a meaningful clinical response to tetrodotoxin as a function of the dose and according to the type of pain, e.g., somatic/visceral. There were a total of six patients treated in each dose level. Note the overall absence of increasing benefit with increasing dose. Journal of Pain and Symptom Management 2007 34, 171-182DOI: (10.1016/j.jpainsymman.2006.11.008) Copyright © 2007 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 4 Mean worst (a), average (b), and current (c) pain intensity scores during the seven-day baseline, four-day treatment period, and through to follow-up Day 15 for patients who experienced no analgesic response, a transient clinically meaningful analgesic response, and a persistent clinically meaningful analgesic response to intramuscular treatment with tetrodotoxin. Journal of Pain and Symptom Management 2007 34, 171-182DOI: (10.1016/j.jpainsymman.2006.11.008) Copyright © 2007 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 5 Mean percent change in the interference of pain on patients' general activity (a), mood (b), walking ability (c), normal work (d), sleep (e), and enjoyment of life (f) following a four-day treatment regimen of intramuscular tetrodotoxin, compared to baseline. Journal of Pain and Symptom Management 2007 34, 171-182DOI: (10.1016/j.jpainsymman.2006.11.008) Copyright © 2007 U.S. Cancer Pain Relief Committee Terms and Conditions

Fig. 6 Sum of days in which patients showed a decrease ≥33% of the descriptors of the Neuropathic Pain Scale (NPS). Journal of Pain and Symptom Management 2007 34, 171-182DOI: (10.1016/j.jpainsymman.2006.11.008) Copyright © 2007 U.S. Cancer Pain Relief Committee Terms and Conditions